Leukemia is a type of cancer that affects blood cells (WBC). There are several types of leukemia each of which affect a specific WBC component. Among the WBC affected, for example, are B cells (e.g., acute lymphoblastic leukemia or "ALL") and granulocytes (e.g., acute myelogenous leukemia or "AML"). Typically, these leukemic cells are identified by (1) various morphological characteristics, (2) poor responsiveness to normal regulatory mechanisms, (3) reduced capacity for cell differentition and (4) the ability to suppress normal myeloid or lymphoid cell growth. For a more detailed, clinical description of leukemia and various forms it may take, see Scientific American, Medicine, vol. 1, 5:VIII (1987).
Among the currently prescribed treatment regimes for leukemia are total body irradiation and chemotherapy. The two treatment regimes, however, pose a clinical dilemma: because leukemia is a cancer of the blood, all of the cells in the blood and all of the cells that arise in bone marrow (and which then migrate to the blood) must be treated (i.e., destroyed or killed) in order to insure destruction of the neoplastic cells. Destruction of all these cells leaves the patient in a severely immunodepressed state which could be as fatal as the leukemia, and thus requires reconstituting the blood components. In such a case, the patient typically is given a marrow transplant or infusion to replace the components destroyed by the treatment.
In both bone marrow and in the blood, there are cells which are known as hematopoietic progenitor (HP) cells. These cells will differentiate in response to colony stimulating factors, and ultimately give rise to the various components of the blood (i.e., granulocytes, monocytes, lymphocytes etc.). Thus, HP cells are the cells of choice when reconstituting the hematopoietic system.
Preferably, HP cells from autologous bone marrow or peripheral blood would be used to reconstitute the hematopoietic system. The use of an autologous source avoids the serious complications, such as graft versus host disease, that arise when non-self tissues are used. A problem arises, however, when an autologous source is used because unless the HP cells are pure, residual tumor cells will isolate with the HP cells and the patient ultimately will relapse with neoplastic disease.
At least one method has been proposed to isolate pure HP cells. Civin et al. identified a monoclonal antibody (anti-My-10, ATCC HB-8483) which is specific for an HP cell surface antigen and may be used to isolate only HP cells from the patient's marrow. See Civin et al., Exp. Hematol., 15:10 (1987). This does nothing to the residual tumor cells in the marrow or blood but acts merely to purify the HP cell component.
Alternatively, it is known that there exists in the blood a subset of the lymphocyte population which will destroy certain tumor cells. This subset has been identified as natural killer (NK) cells. In addition to being effective against certain tumor cells, when activated by a lymphokine, these NK cells increase in their efficiency and range of tumors that can be killed. Recently, Rosenberg, in U.S. Pat. No. 4,690,915, has used lymphokine activated killer (LAK) cells in combination with recombinant interleukin-2 (rIL-2) to treat patients with certain solid tumors in vivo. Rosenberg states, however, that there are significant side effects to this method of treatment, and does not discuss or relate the method of treatment to the in vitro isolation and purification of autologous HP cells.
Accordingly, there has not been described a method for purging a cell preparation from a cancer patient of residual tumor cells using autologous, lymphokine activated cytotoxic cells.